Abstract

The effects of salvinorin A (Salvia divinorum principal ingredient), a potent κ-opioid natural hallucinogen, on learning and memory were investigated. Wistar rats were tested in the 8-arm radial maze, for object recognition and passive avoidance tasks for spatial, episodic, and aversive memory. Attention was assessed using a latent inhibition task. Salvinorin A (80-640 μg/kg subcutaneous [sc]) did not affect short-term memory, but it impaired spatial long-term memory. Episodic and aversive memories were impaired by salvinorin A (160-640 μg/kg). Memory impairment was blocked by the selective κ-opioid receptor antagonist, nor-binaltorphimine ([nor-B]; 0.5-1 mg/kg, intraperitoneal [ip]). Salvinorin A (160 μg/kg) disrupted latent inhibition, after LiCl treatment, such as reduced sucrose intake, suggesting an attention would result in an impairment of cognitive behavior. These findings demonstrate for the first time that salvinorin A has deleterious effects on learning and memory, through a κ-opioid receptor mechanism.